Neoadjuvant Therapy for Hepatocellular Carcinoma

• Status: Recruiting
• Trial end date: 2022-05-30
• Target enrollment: 0
• Participant gender: All

Summary

This study aimed to evaluate the efficacy and the safety of the anti-programmed-death-1 antibody (anti-PD-1) Sintilimab Injection in combination with transarterial chemoembolization with drug-eluting beads(TACE-DEB) in patients with early and intermediate stage hepatocellular carcinoma (HCC) who isn't suitable for primary surgical resection.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Zhejiang University
• Treatments: Chlorotrianisene

Criteria

Inclusion Criteria:

1. Newly histologically confirmed diagnosis of HCC or strictly consistent with the clinical diagnostic criteria for HCC according to AASLD guideline；

2. At least one measurable site of disease as defined by modified RECIST (mRECIST) criteria with spiral CT scan or MRI and has not received local treatment；

3. Patients with BCLC stage A but beyond Milan Criteria and BCLC stage B；

4. Patients should be discussed in multidisciplinary teams and are not eligible for primary resection or local ablation, and tumor burden below 50% of liver volume；

5. ECOG PS score: 0~1 points; Child-Pugh A or B (<=7)；

6. Life expectancy of at least 3 months;

7. Subjects with chronic HBV infection must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy；

8. Adequate blood count, liver-enzymes, and renal function: laboratory test values meet the following requirements within 7 days prior to enrollment (no blood components, cell growth factors, albumin and other corrective therapy drugs are allowed within 14 days prior to laboratory test):

1. absolute neutrophil count, ANC≥1.5×10^9/L, platelet, PLT≥80×10^9/L, hemoglobin, HGB≥8.5 g/dL;

2. total bilirubin, TBIL≤1.5×ULN, alanine aminotransferase, ALT and aspartate transferase, AST≤5×ULN, serum Alb≥28 g/L；

3. creatinine, Cr ≤ 1.5×ULN or clearance of creatinine, CCr≥ 50mL/min, Urine protein<2+;

4. INR≤ 2 and APTT≤ 1.5×ULN.

11. Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial； 10. Patients agreed to join the clinical trial and signed informed consent and are willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.

Exclusion Criteria:

1. Active tuberculosis (TB), who are receiving anti-TB treatment or who received anti-TB treatment within 1 year prior to the first study；Patients with previous or current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, and severe impairment of lung function.

2. Patients With II-IV myocardial ischemia and myocardial infarction, poor control of cardiac arrhythmias; Patients with hypertension who cannot be reduced to the normal range after antihypertensive medication (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg).

3. A history of gastrointestinal perforations and/or fistulas, intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), inflammatory bowel disease or extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea within 6 months; Patients with a history of gastrointestinal bleeding or a clear gastrointestinal bleeding tendency in the past 6 months, such as esophageal varices with bleeding risk, local active ulcer lesions, and fecal occult blood (++).

4. Severe bleeding tendency or coagulation dysfunction, or receiving thrombolytic treatment; Any life-threatening bleeding event that has occurred within the previous 6 months, including the need for blood transfusion, surgery or topical treatment, and continued medication.

5. Autoimmune disease requiring systematic treatment or a history of the disease within 2 years. (such as vitiligo, psoriasis, hair loss or graves' disease).

6. Patients with central nervous system diseases (such as primary brain tumors, stroke, epilepsy, etc.) or central nervous system metastasis or known brain metastasis.

7. Acute or chronic active hepatitis B or C infection; Human immunodeficiency virus (HIV) infection (HIV 1/2 antibody positive); . A severe infection that is active or clinically poorly controlled. Severe infections, including but not limited to hospitalization for infection, bacteremia, or complications of severe pneumonia, occurred 1 month before the first study.

8. Contains fibroblastic layer hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, bile duct carcinoma and other components; Other malignancies were diagnosed within 5 years prior to the first administration, excluding radical basal cell carcinoma of the skin, skin squamous cell carcinoma and/or radical resection of carcinoma in situ. If other malignancies or liver cancer are diagnosed more than 5 years before administration, a pathological or cytological diagnosis of the relapsed and metastatic lesions is required.

9. Previous major surgery (craniotomy, thoracotomy, or laparotomy) within 1 month or unhealed wounds, ulcers, or fractures; Severe arteriovenous fistula; Uncontrolled metabolic disorders or other non-malignant organ or systemic disease or cancer secondary reactions and may result in higher medical risk and/or uncertainty in survival evaluation.

10. Treated with immunosuppressive drugs, live attenuated vaccine, systemic immunostimulant therapy, or any anti-PD-1, anti-PD-L1/L2 antibody or other immunotherapy and experimental drugs within 4 weeks or planned during the study period.

11. Other acute or chronic conditions, psychiatric disorders, or laboratory abnormalities that may increase the risk of study participation or administration of the study drug, or interfere with the interpretation of the study results, and classify patients as ineligible to participate in the study at the discretion of the investigator.

12. Patients with a history of hepatic encephalopathy or a history of liver transplantation or patients preparing for liver transplantation; Pregnant or lactating women; Known to be allergic to any antibody-targeted drug or small-molecular-targeted drug ingredient; Or have a history of severe allergic reactions to other monoclonal antibodies.